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Q02956 (KPCZ_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 152. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein kinase C zeta type

EC=2.7.11.13
Alternative name(s):
nPKC-zeta
Gene names
Name:Prkcz
Synonyms:Pkcz
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length592 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Calcium- and diacylglycerol-independent serine/threonine-protein kinase that functions in phosphatidylinositol 3-kinase (PI3K) pathway and mitogen-activated protein (MAP) kinase cascade, and is involved in NF-kappa-B activation, mitogenic signaling, cell proliferation, cell polarity, inflammatory response and maintenance of long-term potentiation (LTP). Upon lipopolysaccharide (LPS) treatment in macrophages, or following mitogenic stimuli, functions downstream of PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently of RAF1 activation. Required for insulin-dependent activation of AKT3, but may function as an adapter rather than a direct activator. Upon insulin treatment may act as a downstream effector of PI3K and contribute to the activation of translocation of the glucose transporter SLC2A4/GLUT4 and subsequent glucose transport in adipocytes. In EGF-induced cells, binds and activates MAP2K5/MEK5-MAPK7/ERK5 independently of its kinase activity and can activate JUN promoter through MEF2C. Through binding with SQSTM1/p62, functions in interleukin-1 signaling and activation of NF-kappa-B with the specific adapters RIPK1 and TRAF6. Participates in TNF-dependent transactivation of NF-kappa-B by phosphorylating and activating IKBKB kinase, which in turn leads to the degradation of NF-kappa-B inhibitors. In migrating astrocytes, forms a cytoplasmic complex with PARD6A and is recruited by CDC42 to function in the establishment of cell polarity along with the microtubule motor and dynein. In association with FEZ1, stimulates neuronal differentiation in PC12 cells. Is necessary and sufficient for LTP maintenance in hippocampal CA1 pyramidal cells By similarity. In inflammatory response, is required for the T-helper 2 (Th2) differentiation process, including interleukins production, efficient activation of JAK1 and the subsequent phosphorylation and nuclear translocation of STAT6. May be involved in development of allergic airway inflammation (asthma), a process dependent on Th2 immune response. In NF-kappa-B-mediated inflammatory response, can relieve the SETD6-dependent repression of NF-kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'. Ref.5 Ref.6

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Atypical PKCs (PRKCI and PRKCZ) exhibit an elevated basal enzymatic activity (that may be due to the interaction with SMG1 or SQSTM1) and are not regulated by diacylglycerol, phosphatidylserine, phorbol esters or calcium ions. Two specific sites, Thr-410 (activation loop of the kinase domain) and Thr-560 (turn motif), need to be phosphorylated for its full activation. Phosphatidylinositol 3,4,5-trisphosphate might be a physiological activator By similarity.

Subunit structure

Interacts directly with SQSTM1. Forms a ternary complex with SQSTM1 and KCNAB2. Forms another ternary complex with SQSTM1 and GABRR3. Forms a complex with SQSTM1 and MAP2K5 By similarity. Interacts with PARD6A, PARD6B and PARD6G. Part of a complex with PARD3, PARD6A or PARD6B or PARD6G and CDC42 or RAC1. Interacts with ADAP1/CENTA1. Interacts (via the protein kinase domain) with WWC1. Forms a tripartite complex with WWC1 and DDR1, but predominantly in the absence of collagen. Interacts with PDPK1 (via N-terminal region) By similarity. Ref.4

Subcellular location

Cytoplasm By similarity. Endosome By similarity. Cell junction By similarity. Note: In the retina, localizes in the terminals of the rod bipolar cells. Associated with endosomes. Presence of KRIT1, CDH5 and RAP1B is required for its localization to the cell junction By similarity.

Domain

The C1 domain does not bind the diacylglycerol (DAG).

The OPR domain mediates mutually exclusive interactions with SQSTM1 and PARD6B By similarity.

Post-translational modification

CDH5 is required for its phosphorylation at Thr-410. Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by the apoptotic C-terminal cleavage product of PKN2. Phosphorylation at Thr-410 by PI3K activates the kinase By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.

Contains 1 AGC-kinase C-terminal domain.

Contains 1 OPR domain.

Contains 1 phorbol-ester/DAG-type zinc finger.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processInflammatory response
   Cellular componentCell junction
Cytoplasm
Endosome
   DomainZinc-finger
   LigandATP-binding
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactin cytoskeleton reorganization

Inferred from electronic annotation. Source: Ensembl

activation of phospholipase D activity

Inferred from electronic annotation. Source: Ensembl

activation of protein kinase B activity

Inferred from electronic annotation. Source: Ensembl

cell migration

Inferred from electronic annotation. Source: Ensembl

establishment of cell polarity

Inferred from sequence or structural similarity. Source: UniProtKB

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

insulin receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

long-term memory

Inferred from electronic annotation. Source: Ensembl

long-term synaptic potentiation

Inferred from sequence or structural similarity. Source: UniProtKB

membrane hyperpolarization

Inferred from electronic annotation. Source: Ensembl

microtubule cytoskeleton organization

Inferred from mutant phenotype PubMed 15882626. Source: MGI

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of hydrolase activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of insulin receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of peptidyl-tyrosine phosphorylation

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein complex assembly

Inferred from electronic annotation. Source: Ensembl

neuron projection extension

Inferred from genetic interaction PubMed 19668197. Source: MGI

peptidyl-serine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of ERK1 and ERK2 cascade

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of NF-kappaB transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of T-helper 2 cell cytokine production

Inferred from mutant phenotype Ref.5. Source: UniProtKB

positive regulation of T-helper 2 cell differentiation

Inferred from mutant phenotype Ref.5. Source: UniProtKB

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell-matrix adhesion

Inferred from electronic annotation. Source: Ensembl

positive regulation of excitatory postsynaptic membrane potential

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of glucose import

Inferred from electronic annotation. Source: Ensembl

positive regulation of insulin receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of interleukin-10 secretion

Inferred from mutant phenotype Ref.5. Source: UniProtKB

positive regulation of interleukin-13 secretion

Inferred from mutant phenotype Ref.5. Source: UniProtKB

positive regulation of interleukin-4 production

Inferred from mutant phenotype Ref.5. Source: UniProtKB

positive regulation of interleukin-5 secretion

Inferred from mutant phenotype Ref.5. Source: UniProtKB

protein heterooligomerization

Inferred from electronic annotation. Source: Ensembl

protein kinase C signaling

Inferred from electronic annotation. Source: Ensembl

protein localization to plasma membrane

Inferred from mutant phenotype PubMed 16455755. Source: MGI

protein phosphorylation

Inferred from direct assay PubMed 14730360. Source: MGI

vesicle transport along microtubule

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentapical cortex

Inferred from direct assay PubMed 15950600. Source: MGI

apical plasma membrane

Inferred from direct assay PubMed 20551175. Source: MGI

axon hillock

Inferred from direct assay PubMed 19668197. Source: MGI

cell cortex

Inferred from direct assay PubMed 15950600. Source: MGI

cell leading edge

Inferred from electronic annotation. Source: Ensembl

cell-cell junction

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from direct assay PubMed 10882525PubMed 12871585PubMed 14730360. Source: MGI

cytosol

Inferred from electronic annotation. Source: Ensembl

endosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

membrane raft

Inferred from electronic annotation. Source: Ensembl

microtubule organizing center

Inferred from genetic interaction PubMed 19668197. Source: MGI

myelin sheath abaxonal region

Inferred from direct assay PubMed 20237282. Source: BHF-UCL

nuclear envelope

Inferred from direct assay PubMed 10882525. Source: MGI

nuclear matrix

Inferred from direct assay PubMed 10882525. Source: MGI

nucleus

Inferred from direct assay PubMed 10882525. Source: MGI

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from direct assay PubMed 10882525. Source: MGI

protein complex

Inferred from direct assay PubMed 16510873. Source: MGI

tight junction

Inferred from direct assay PubMed 15775979PubMed 15950600. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

potassium channel regulator activity

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction Ref.6. Source: UniProtKB

protein kinase C activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein kinase activity

Inferred from direct assay PubMed 14730360. Source: MGI

protein serine/threonine kinase activity

Inferred from direct assay Ref.6. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 592592Protein kinase C zeta type
PRO_0000055702

Regions

Domain15 – 9884OPR
Domain252 – 518267Protein kinase
Domain519 – 59072AGC-kinase C-terminal
Zinc finger130 – 18051Phorbol-ester/DAG-type
Nucleotide binding258 – 2669ATP By similarity
Region79 – 14567Interaction with SQSTM1 By similarity

Sites

Active site3761Proton acceptor By similarity
Binding site2811ATP By similarity

Amino acid modifications

Modified residue4101Phosphothreonine; by PDPK1 and PI3K By similarity
Modified residue5601Phosphothreonine By similarity

Experimental info

Sequence conflict1971D → G in AAA39983. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q02956 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 690AD891C25BC311

FASTA59267,682
        10         20         30         40         50         60 
MPSRTDPKMD RSGGRVRLKA HYGGDILITS VDAMTTFKDL CEEVRDMCGL HQQHPLTLKW 

        70         80         90        100        110        120 
VDSEGDPCTV SSQMELEEAF RLVCQGRDEV LIIHVFPSIP EQPGMPCPGE DKSIYRRGAR 

       130        140        150        160        170        180 
RWRKLYRANG HLFQAKRFNR GAYCGQCSER IWGLSRQGYR CINCKLLVHK RCHVLVPLTC 

       190        200        210        220        230        240 
RRHMDSVMPS QEPPVDDKND GVDLPSEETD GIAYISSSRK HDNIKDDSED LKPVIDGVDG 

       250        260        270        280        290        300 
IKISQGLGLQ DFDLIRVIGR GSYAKVLLVR LKKNDQIYAM KVVKKELVHD DEDIDWVQTE 

       310        320        330        340        350        360 
KHVFEQASSN PFLVGLHSCF QTTSRLFLVI EYVNGGDLMF HMQRQRKLPE EHARFYAAEI 

       370        380        390        400        410        420 
CIALNFLHER GIIYRDLKLD NVLLDADGHI KLTDYGMCKE GLGPGDTTST FCGTPNYIAP 

       430        440        450        460        470        480 
EILRGEEYGF SVDWWALGVL MFEMMAGRSP FDIITDNPDM NTEDYLFQVI LEKPIRIPRF 

       490        500        510        520        530        540 
LSVKASHVLK GFLNKDPKER LGCRPQTGFS DIKSHAFFRS IDWDLLEKKQ TLPPFQPQIT 

       550        560        570        580        590 
DDYGLDNFDT QFTSEPVQLT PDDEDVIKRI DQSEFEGFEY INPLLLSAEE SV 

« Hide

References

« Hide 'large scale' references
[1]"The cDNA sequence, expression pattern and protein characteristics of mouse protein kinase C-zeta."
Goodnight J., Kazanietz M.G., Blumberg P.M., Mushinski F.J., Mischak H.
Gene 122:305-311(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[3]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42."
Joberty G., Petersen C., Gao L., Macara I.G.
Nat. Cell Biol. 2:531-539(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PARD6B.
Tissue: Embryo.
[5]"Control of T helper 2 cell function and allergic airway inflammation by PKCzeta."
Martin P., Villares R., Rodriguez-Mascarenhas S., Zaballos A., Leitges M., Kovac J., Sizing I., Rennert P., Marquez G., Martinez-A C., Diaz-Meco M.T., Moscat J.
Proc. Natl. Acad. Sci. U.S.A. 102:9866-9871(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN INFLAMMATORY RESPONSE.
[6]"Lysine methylation of the NF-kappaB subunit RelA by SETD6 couples activity of the histone methyltransferase GLP at chromatin to tonic repression of NF-kappaB signaling."
Levy D., Kuo A.J., Chang Y., Schaefer U., Kitson C., Cheung P., Espejo A., Zee B.M., Liu C.L., Tangsombatvisit S., Tennen R.I., Kuo A.Y., Tanjing S., Cheung R., Chua K.F., Utz P.J., Shi X., Prinjha R.K. expand/collapse author list , Lee K., Garcia B.A., Bedford M.T., Tarakhovsky A., Cheng X., Gozani O.
Nat. Immunol. 12:29-36(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M94632 mRNA. Translation: AAA39983.1.
AL670413, AL670227 Genomic DNA. Translation: CAM20048.1.
AL670227, AL670413 Genomic DNA. Translation: CAM20648.1.
CH466594 Genomic DNA. Translation: EDL15000.1.
CCDSCCDS19026.1.
PIRJC1480.
RefSeqNP_032886.2. NM_008860.3.
UniGeneMm.28561.

3D structure databases

ProteinModelPortalQ02956.
SMRQ02956. Positions 13-182, 184-584.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202203. 10 interactions.
IntActQ02956. 3 interactions.
MINTMINT-98101.

PTM databases

PhosphoSiteQ02956.

Proteomic databases

MaxQBQ02956.
PaxDbQ02956.
PRIDEQ02956.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000030922; ENSMUSP00000030922; ENSMUSG00000029053.
GeneID18762.
KEGGmmu:18762.
UCSCuc008wdc.1. mouse.

Organism-specific databases

CTD5590.
MGIMGI:97602. Prkcz.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00750000117322.
HOGENOMHOG000233033.
HOVERGENHBG108317.
InParanoidA2AD76.
KOK06069.
OMARCHVLVP.
OrthoDBEOG7HF1J3.
TreeFamTF102004.

Enzyme and pathway databases

BRENDA2.7.11.13. 3474.

Gene expression databases

ArrayExpressQ02956.
BgeeQ02956.
CleanExMM_PRKCZ.
GenevestigatorQ02956.

Family and domain databases

InterProIPR000961. AGC-kinase_C.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR000270. OPR_PB1.
IPR012233. PKC_zeta.
IPR017892. Pkinase_C.
IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERPTHR24357:SF60. PTHR24357:SF60. 1 hit.
PfamPF00130. C1_1. 1 hit.
PF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFPIRSF000554. PKC_zeta. 1 hit.
PRINTSPR00008. DAGPEDOMAIN.
SMARTSM00109. C1. 1 hit.
SM00666. PB1. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS00479. ZF_DAG_PE_1. 1 hit.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio294953.
PROQ02956.
SOURCESearch...

Entry information

Entry nameKPCZ_MOUSE
AccessionPrimary (citable) accession number: Q02956
Secondary accession number(s): A2AD76
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 152 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot